Chronic stress is implicated in the pathogenesis of cardiovascular disease, the metabolic syndrome, neurodegeneration, depression and other psychiatric disorders, and inflammatory diseases. Skeletal myopathy and neuronal cell atrophy are common complications of endogenous and exogenous glucocorticoid excess; yet the underlying mechanisms remain unclear and targeted therapeutic interventions are limited. Mitochondria play a pivotal role in cell homeostasis, housing multiple metabolic pathways that result in energy production in the form of ATP. They also generate most cellular reactive oxygen species (ROS) and regulate programmed cell death, serving as a gatekeeper for apoptosis. Not surprisingly, primary or secondary mitochondrial dysfunction have been associated with the pathogenesis of conditions such as obesity, diabetes, cancer, neurodegeneration, cardiomyopathy, depression and aging, of obvious public health significance. Patients with the aforementioned diseases commonly use wide CAM modalities. To identify pathways involved in glucocorticoid- or stress-induced mitochondrial dysfunction in skeletal muscle, we investigated the transcriptional adaptations that follow exposure of primary human skeletal myocytes to dexamethasone by screening 501 mitochondria-related genes with a custom-made human cDNA microarray chip (hMitChip, NICHD). We reported that the catecholamine-metabolizing enzyme MAO-A is a major target for glucocorticoids in human skeletal muscle cells. MAO catalyzes the oxidative deamination of neuroactive, vasoactive (serotonin, dopamine, catecholamines), or dietary (tyramine) amines and xenobiotics, releasing reactive aldehydes and H202. MAO-A activation by glucocorticoids with subsequent excess hydrogen peroxide production could represent a novel pathway for glucocorticoid-induced oxidative tissue damage, and MAO-inhibitors or other allopathic and CAM interventions aimed at different components of that pathway may serve as therapeutic agents. Genetic studies have linked MAO-A and MAO-B to various aspects of human behavior, and environmental interactions modulate the expression of certain MAO-A polymorphisms; however, the hormonal regulation of their expression in humans remains unexplored. We examined the effects of adrenal, gonadal and neurosteroids, in addition to glucocorticoids, on MAO expression in human fetal astrocytes. We hypothesized that estrogen, progesterone, DHEA and/or other neurosteroids (allopreganolone, THDOC) may elicit effectson on MAO expression opposite to those of glucocorticoids .